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000136022 1001_ $$00000-0001-6461-6953$$aCulina, Slobodan$$b0
000136022 245__ $$aIslet-reactive CD8+ T cell frequencies in the pancreas, but not in blood, distinguish type 1 diabetic patients from healthy donors.
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000136022 520__ $$aThe human leukocyte antigen-A2 (HLA-A2)-restricted zinc transporter 8186-194 (ZnT8186-194) and other islet epitopes elicit interferon-γ secretion by CD8+ T cells preferentially in type 1 diabetes (T1D) patients compared with controls. We show that clonal ZnT8186-194-reactive CD8+ T cells express private T cell receptors and display equivalent functional properties in T1D and healthy individuals. Ex vivo analyses further revealed that CD8+ T cells reactive to ZnT8186-194 and other islet epitopes circulate at similar frequencies and exhibit a predominantly naïve phenotype in age-matched T1D and healthy donors. Higher frequencies of ZnT8186-194-reactive CD8+ T cells with a more antigen-experienced phenotype were detected in children versus adults, irrespective of disease status. Moreover, some ZnT8186-194-reactive CD8+ T cell clonotypes were found to cross-recognize a Bacteroides stercoris mimotope. Whereas ZnT8 was poorly expressed in thymic medullary epithelial cells, variable thymic expression levels of islet antigens did not modulate the peripheral frequency of their cognate CD8+ T cells. In contrast, ZnT8186-194-reactive cells were enriched in the pancreata of T1D patients versus nondiabetic and type 2 diabetic individuals. Thus, islet-reactive CD8+ T cells circulate in most individuals but home to the pancreas preferentially in T1D patients. We conclude that the activation of this common islet-reactive T cell repertoire and progression to T1D likely require defective peripheral immunoregulation and/or a proinflammatory islet microenvironment.
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000136022 7001_ $$aAfonso, Georgia$$b2
000136022 7001_ $$00000-0002-7403-6239$$aCerosaletti, Karen$$b3
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000136022 7001_ $$00000-0002-7526-628X$$aKuranda, Klaudia$$b6
000136022 7001_ $$00000-0002-6251-3069$$aNigi, Laura$$b7
000136022 7001_ $$00000-0001-8009-5959$$aEugster, Anne$$b8
000136022 7001_ $$00000-0002-1449-8036$$aØsterbye, Thomas$$b9
000136022 7001_ $$00000-0001-8721-288X$$aMaugein, Alicia$$b10
000136022 7001_ $$aMcLaren, James E$$b11
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000136022 7001_ $$00000-0002-1017-1845$$aLarger, Etienne$$b13
000136022 7001_ $$00000-0003-4938-5610$$aBeressi, Jean-Paul$$b14
000136022 7001_ $$aLissina, Anna$$b15
000136022 7001_ $$aAppay, Victor$$b16
000136022 7001_ $$00000-0001-5605-3812$$aDavidson, Howard W$$b17
000136022 7001_ $$aBuus, Søren$$b18
000136022 7001_ $$aPrice, David A$$b19
000136022 7001_ $$00000-0003-2868-5155$$aKuhn, Matthias$$b20
000136022 7001_ $$00000-0002-8704-4713$$aBonifacio, Ezio$$b21
000136022 7001_ $$00000-0003-4535-3152$$aBattaglia, Manuela$$b22
000136022 7001_ $$aCaillat-Zucman, Sophie$$b23
000136022 7001_ $$aDotta, Francesco$$b24
000136022 7001_ $$aScharfmann, Raphael$$b25
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000136022 7001_ $$00000-0002-9846-8861$$aMallone, Roberto$$b27
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000136022 7001_ $$aCarel, Jean-Claude$$b29
000136022 7001_ $$aTubiana-Rufi, Nadia$$b30
000136022 7001_ $$aMartinerie, Laetitia$$b31
000136022 7001_ $$aPoidvin, Amélie$$b32
000136022 7001_ $$aJacqzAigrain, Evelyne$$b33
000136022 7001_ $$aCorvez, Laurence$$b34
000136022 7001_ $$aBerruer, Véronique$$b35
000136022 7001_ $$aGautier, Jean-François$$b36
000136022 7001_ $$aBaz, Baz$$b37
000136022 7001_ $$aHaddadi, Nassima$$b38
000136022 7001_ $$aAndreelli, Fabrizio$$b39
000136022 7001_ $$aAmouyal, Chloé$$b40
000136022 7001_ $$aJaqueminet, Sophie$$b41
000136022 7001_ $$aBourron, Olivier$$b42
000136022 7001_ $$aDasque, Eric$$b43
000136022 7001_ $$aHartemann, Agnès$$b44
000136022 7001_ $$aLemoine-Yazigi, Amal$$b45
000136022 7001_ $$aDubois-Laforgue, Danièle$$b46
000136022 7001_ $$aTravert, Florence$$b47
000136022 7001_ $$aFeron, Marilyne$$b48
000136022 7001_ $$aRolland, Patrice$$b49
000136022 7001_ $$aVignali, Valérie$$b50
000136022 7001_ $$aMarre, Michel$$b51
000136022 7001_ $$aChanson, Philippe$$b52
000136022 7001_ $$aBriet, Claire$$b53
000136022 7001_ $$aGuillausseau, Pierre-Jean$$b54
000136022 7001_ $$aAit-Bachir, Leila$$b55
000136022 7001_ $$aCollet, Carole$$b56
000136022 7001_ $$aBeziaud, Frédéric$$b57
000136022 7001_ $$aDesforges-Bullet, Virginie$$b58
000136022 7001_ $$aPetit-Aubert, Gwenaelle$$b59
000136022 7001_ $$aChristin-Maitre, Sophie$$b60
000136022 7001_ $$aFève, Bruno$$b61
000136022 7001_ $$aVatier, Camille$$b62
000136022 7001_ $$aBourcigaux, Nathalie$$b63
000136022 7001_ $$aLautridou, Céline$$b64
000136022 7001_ $$aLahlou, Najiba$$b65
000136022 7001_ $$aBakouboula, Prissile$$b66
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000136022 7001_ $$aGagnerault, Marie-Claude$$b70
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